"An agent that produces temporary physiological or mental effects, or both, which will render individuals incapable of concerted effort in the performance of their assigned duties."

Lethal agents are primarily intended to kill, but incapacitating agents can also kill if administered in a potent enough dose, or in certain scenarios.

The term "incapacitation," when used in a general sense, is not equivalent to the term "disability" as used in occupational medicine and denotes the inability to perform a task because of a quantifiable physical or mental impairment. In this sense, any of the chemical warfare agents may incapacitate a victim; however, again by the military definition of this type of agent, incapacitation refers to impairments that are temporary and nonlethal. Thus, riot-control agents are incapacitating because they cause temporary loss of vision due to blepharospasm, but they are not considered military incapacitants because the loss of vision does not last long. Although incapacitation may result from physiological changes such as mucous membrane irritation, diarrhea, or hyperthermia, the term "incapacitating agent" as militarily defined refers to a compound that produces temporary and nonlethal impairment of military performance by virtue of its psychobehavioral or CNS effects.

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The use of chemicals to induce altered states of mind dates to antiquity and includes the use of plants such as thornapple (Datura stramonium) that contain combinations of anticholinergic alkaloids. The use of nonlethal chemicals to render an enemy force incapable of fighting dates back to at least 600 B.C. when Solon's soldiers threw hellebore roots into streams supplying water to enemy troops, who then developed diarrhea. In 184 B.C., Hannibal's army used belladonna plants to induce disorientation,[citation needed] and the Bishop of Münster in A.D. 1672 attempted to use belladonna-containing grenades in an assault on the city of Groningen.[2] In 1881, members of a railway surveying expedition crossing Tuareg territory in North Africa ate dried dates that tribesmen had apparently deliberately contaminated with Hyoscyamus falezlez. In 1908, 200 French soldiers in Hanoi became delirious and experienced hallucinations after being poisoned with a related plant. More recently, accusations of Soviet use of incapacitating agents internally and in Afghanistan were never substantiated. (See also the Moscow theatre siege case, below).

Following World War II, the United States military investigated a wide range of possible nonlethal, psychobehavioral, chemical incapacitating agents to include psychedelic indoles such as lysergic acid diethylamide (LSD-25) and the Tetrahydrocannabinol derivative DMHP, certain tranquilizers, as well as several glycolate anticholinergics. One of the anticholinergic compounds, 3-quinuclidinyl benzilate, was assigned the NATO code BZ and was weaponized beginning in the 1960s for possible battlefield use. Although BZ figured prominently in the plot of the 1990 movie, Jacob's Ladder, as the compound responsible for hallucinations and violent deaths in a fictitious American battalion in Vietnam, this agent never saw operational use. Destruction of American stockpiles began in 1988 and is now complete.

There is one documented case of incapacitating agents being used in recent years. In 2002, Chechen terrorists took a large number of hostages in the Moscow theatre siege, and threatened to blow up the entire theatre if any attempt was made to break the siege. An incapacitating agent was used to disable the terrorists whilst the theatre was stormed by special forces. However, the incapacitating agent, unknown at that time, caused many of the hostages to die. The situation was not helped by the fact that the authorities kept the nature of the incapacitating agent secret from doctors trying to treat its victims. At the time, the gas was reported to be an unknown incapacitating agent called "Kolokol-1". The Russian Health Minister Yuri Shevchenko later stated that the incapacitating agent used in the storming of the Moscow theatre siege was a fentanyl derivative.